chr13-28386456-T-A

Variant names:

• chr13-28386456-T-A
• rs3751397
• ENST00000615840.5:c.*3245A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000615840.5(FLT1):​c.*3245A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,041,944 control chromosomes in the GnomAD database, including 140,888 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (15684 hom., cov: 32)
  • Exomes 𝑓: 0.53 (125204 hom.)
• Consequence: FLT1 ENST00000615840.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 14 publications found

Genes affected

FLT1 (HGNC:3763): (fms related receptor tyrosine kinase 1) This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.[provided by RefSeq, May 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615840.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	NM_002019.4	MANE Select	c.1970-1425A>T		intron	N/A	NP_002010.2
	FLT1	NM_001159920.2		c.*3245A>T		3_prime_UTR	Exon 13 of 13	NP_001153392.1
	FLT1	NM_001160030.2		c.1970-1425A>T		intron	N/A	NP_001153502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLT1	ENST00000615840.5	TSL:1	c.*3245A>T		3_prime_UTR	Exon 13 of 13	ENSP00000484039.1
	FLT1	ENST00000282397.9	TSL:1 MANE Select	c.1970-1425A>T		intron	N/A	ENSP00000282397.4
	FLT1	ENST00000541932.5	TSL:1	c.1970-1425A>T		intron	N/A	ENSP00000437631.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65715 AN: 151916 Hom.: 15678 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.527 AC: 469019 AN: 889910 Hom.: 125204 Cov.: 25 AF XY: 0.529 AC XY: 217572 AN XY: 411246

African (AFR) AF: 0.198 AC: 3665 AN: 18534

American (AMR) AF: 0.496 AC: 1372 AN: 2764

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 4787 AN: 8942

East Asian (EAS) AF: 0.561 AC: 6958 AN: 12392

South Asian (SAS) AF: 0.485 AC: 8209 AN: 16928

European-Finnish (FIN) AF: 0.447 AC: 144 AN: 322

Middle Eastern (MID) AF: 0.493 AC: 976 AN: 1978

European-Non Finnish (NFE) AF: 0.536 AC: 426781 AN: 795990

Other (OTH) AF: 0.503 AC: 16127 AN: 32060

GnomAD4 genome AF: 0.432 AC: 65739 AN: 152034 Hom.: 15684 Cov.: 32 AF XY: 0.432 AC XY: 32091 AN XY: 74318

African (AFR) AF: 0.215 AC: 8925 AN: 41494

American (AMR) AF: 0.482 AC: 7348 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3466

East Asian (EAS) AF: 0.536 AC: 2764 AN: 5156

South Asian (SAS) AF: 0.480 AC: 2314 AN: 4816

European-Finnish (FIN) AF: 0.451 AC: 4758 AN: 10554

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35944 AN: 67972

Other (OTH) AF: 0.476 AC: 1006 AN: 2114

Alfa AF: 0.470 Hom.: 2171

Bravo AF: 0.427

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3751397; hg19: chr13-28960593;